The overall aims of this research grant are to investigate the role of histamine as a regulator immune function. While the physiologic role of histamine as a mediator of allergic reactions is well known, its ability to modulate humoral or cellular immune reactions has only recently been appreciated. The results derived from this line of investigation may provide a better insight into the basic control mechanisms of immunity and might lead to improved forms of therapy for patients with immunologic malfunction. The goals for this current year include: 1. Further studies concerning the lymphokine, histamine induced suppressor factor or HSF, in terms of its physical chemical characterization, defining the subset of lymphocytes that elaborate this factor, and its mechanism of action. 2). An investigation into a newly described lymphokine, histamine releasing factors or HRF, in terms of its physical chemical characterization, defining the subpopulation of cells responsible for its production, its mechanism of action, and its inter-relationship with HSF. 3). In vivo studies in a guinea pig model which the ability of selective histamine antagonists and agonists to alter both humoral and cellular immune responses will be investigated. Cell transfer experiments will be employed to determine what effect the absence of cells bearing histamine receptors will have on a given response. We also hope to evaluate the in vivo effects of some of the above lymphokines produced in vitro.